Flint Lockwood dreams about becoming an inventor. As a child, he shows his class his latest invention: spray-on shoes, meaning no more untied shoe laces. He sprays black gummi-textured shoes onto his feet, but can't get them off and his class laughs at him. At home, he tries everything to get the shoes off, but nothing is working. His parents are outside his room, trying to comfort him. Flint’s father can only talk to him using fishing metaphors, which Flint doesn't understand. His mother does better, giving him a real lab coat (which is huge on him) and telling him he'll grow into it, and into a great inventor.

Over the years, Flint creates lots of unsuccessful inventions, including a remote-controlled television (a TV on legs), a monkey thought translator, and a flock of ratbirds. Now Flint is grown up, and his mother passed away some time ago. His father still doesn't understand him, wishing Flint would give up on inventions and work in the family bait and tackle shop. Flint is still wearing his spray on shoes. He dreams about creating an invention that will save their town, a tiny island called Swallow Falls. The town survived based on their sardine industry, but the business died once everybody realized sardines are gross.

Flint’s new invention is designed to convert water into food, but he doesn't have enough power in his backyard laboratory to make it work. Meanwhile, the power-hungry mayor is unveiling his plan to save the town - an amusement park called Sardine Land. A news station has sent an intern, Sam Sparks, to cover the unimportant event. While the whole town is at the unveiling, Flint sneaks up to the power lines to turn on his invention, which is set to cheeseburgers. The machine overloads and shoots off like a rocket, with Flint hanging on behind it. It zooms around town, wrecking Sardine Land, and finally shooting up into the sky. Everybody is furious at Flint, and he goes to hide under the docks with his best friend Steve (the monkey he designed the thought translator for). Sam’s first news report was wrecked by Flint’s machine, and she also goes to mope on the docks. She meets Flint, who is immediately enamored because she understands and is impressed by his inventions (the spray on shoes and monkey translator). Flint is still depressed about his latest failure, but suddenly mustard, a pickle, and a slice of cheese fall from the sky. The entire town watches in amazement as giant clouds shaped like burgers roll in, showering them with cheeseburgers. Everybody loves the invention.

The mayor, who is constantly eating, tells Flint that his invention can save the town. Sam also begs Flint to keep making food, so she can be a real weathergirl. Flint is uneasy at first, but is persuaded. He rushes to make a satellite in his lab, with which he can send orders from his computer for more food. We also learn how the machine works - it sucks in water from the clouds through the top, uses microwave beams to mutate the water molecules into any kind of food, then sends the food out the bottom. Flint has a dange-ometer in case the food mutates too much, but he doesn't think much of it. The town goes crazy for the food, flooding Flint with requests. The leftover food is catapulted into a mountain, which is surrounded by a dam just overlooking the town. They also change the town name to Chewandswallow.

The mayor (who grows fatter throughout the movie) wants to make the town a tourist attraction, advertising all over the world, and planning a grand opening in one month. Everybody loves what is happening, except Flint’s father. He still isn't sure about the invention, and he’s not good at talking to Flint. He never tells Flint that he loves him and that he’s proud of him. Meanwhile, the food from the sky starts getting bigger and bigger. We also see that the machine in the sky is getting more and more coated with food. Alarmed, Flint runs tests and sees that the food is getting too mutated. Because the town has been using it too much, the machine is sucking up more and more precipitation through the clouds, emitting more microwave beams, and causing more mutations. The dange-ometer has moved up from green to yellow. However, it’s the night before the grand opening for the tourists the mayor tells Flint not to worry and to keep going. He says that everybody will like Flint because of the invention, and Flint listens to him. The mayor orders spaghetti and meatballs for the next day.

Sam, who is actually very intelligent and knowledgeable about weather, checks a Doppler machine and sees a huge storm on its way. She tries to warn Flint, but he doesn't listen to her. The town is packed with tourists from around the world, eating the assorted giant food falling from the sky. The townspeople have all been gorging themselves throughout the movie. As Flint is just about to cut the ceremonial ribbon, the skies turn red and a spaghetti tornado blows through, ripping the town apart. Giant meatballs also fall and smash everything. Flint runs (or is blown through the tornado) home to turn off the machine via the satellite. He loses his lab coat on the way. When he gets to his lab, the mayor (now so obese he’s in a motorized chair) is already there, ordering dinner through the computer. Flint tries to hit the kill switch, but the mayor throws a giant radish and destroys the satellite. Flint asks what he just ordered for dinner, and the mayor nervously replies, “A Las Vegas style all-you-can-eat buffet.”

The food storms have grown so large that the entire world is being pummeled with giant food. Flint has given up, lying in the bottom of a trash can. His father, who found Flint’s lab coat, gives it back to him and Flint is back on his feet. Because the satellite was destroyed, Flint has to fly up to the machine up in the sky to manually shut it down with the kill code. He apologizes to Sam, who agrees to go with him. The machine is now surrounded by an enormous meatball made up of food. Furthermore, the food has mutated so much that it is now “super food” that is sentient and defends the machine. While being attacked by food, Flint loses the flash drive containing the kill code and calls to ask his father to email the file to his cell phone. His father has no idea how to do that, but Flint talks him through it. Flint and Sam fight their way to the center of the giant food-mass to reach the machine. Unfortunately, Sam gets pricked by peanut brittle (she’s allergic to peanuts) and has to return to their flying car. Flint gets to the machine, but his father accidentally sent an internet video instead of the kill code. He sees his shoes (still the spray-on) that can never come off, and is inspired to spray the bottom of the machine, where the food comes out. The machine explodes and all the food-weather disappears. Meanwhile, the town of Chewandswallow has been evacuating on boats made of food. The dam burst and buried the town with leftovers. Sam and Flint’s father think Flint didn't make it, but he descends with the help of a flock of ratbirds. Sam and Flint kiss and the townspeople cheer.

End credits cartoons - we see the town made a new Chewandswallow 2 using the giant food. Flint and his father go into business, using his spray-on shoes as roof sealant. The mayor, who had also left on a food boat, ate his boat and sinks in the ocean. At the very end, everybody sprays the sealant upwards to create another ozone layer.